Anavex Life Sciences Corp (AVXL)

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Cocaine and the sigma-1 receptor.

How does cocaine effect the sigma-1 protein receptor?

Well, I didn’t even know that it did, that there is a cocaine/sigma-1 receptor interaction. I looked it up (“cocaine, sigma-1 receptor”); found (among others) this paper (2005):
Cocaine up-regulates Fra-2 and sigma-1 receptor gene and protein expression in brain regions involved in addiction and reward
https://pubmed.ncbi.nlm.nih.gov/15879001/

I’ll let others explain the finer details of this interaction. It appears that a sigma-1 antagonist used in the study (opposite to blarcamesine, which is an “agonist,” an activator), by its disabling of the sigma-1 receptor protein, reduced or stopped the effects of cocaine. “All of these cocaine-induced effects were prevented by BD1063,” the sigma-1 receptor antagonist.

Blarcamesine activates the sigma-1 receptor protein; the opposite of the antagonist used in the study. In my quick look at the phenomenon, it doesn’t appear (to me, at least) that blarcamesine could play any therapeutic role in cocaine use or addiction. (Well, perhaps blarcamesine, binding to the sigma-1 protein, could competitively exclude cocaine’s binding to it? I don’t know.)

The paper does show, however, that the sigma-1 receptor controls or effects a diversity of downstream processes in the cell. Sigma-1 is not a one-trick pony. It’s a master control or modulator of a wide diversity of cellular processes, which when activated by blarcamesine can be restored or enhanced, bringing normal, healthful operation of the cell (primarily neurons) in otherwise diseased cells.